Transcription factor II H

general transcription factor IIH, polypeptide 1, 62kDa
Identifiers
Symbol	GTF2H1
Alt. symbols	BTF2
Entrez	2965
HUGO	4655
OMIM	189972
RefSeq	NM_005316
UniProt	P32780
Other data
Locus	Chr. 11 p15.1-p14

general transcription factor IIH, polypeptide 2, 44kDa
Identifiers
Symbol	GTF2H2
Alt. symbols	BTF2, TFIIH, BTF2P44, T-BTF2P44
Entrez	2966
HUGO	4656
OMIM	601748
RefSeq	NM_001515
UniProt	Q13888
Other data
Locus	Chr. 5 q12.2-13.3

general transcription factor IIH, polypeptide 3, 34kDa
Identifiers
Symbol	GTF2H3
Alt. symbols	BTF2, TFIIH
Entrez	2967
HUGO	4657
OMIM	601750
RefSeq	NM_001516
UniProt	Q13889
Other data
Locus	Chr. 12 q24.31

Transcription factor II Human (Transcription Factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair pathways. TFIIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named as TFIIH in 1992.^[1]^[2]

TFIIH consists of ten subunits, 7 of which (XPD, XPB, p62, p52, p44, p34 and TTDA) form the core complex. The cyclin activating kinase-subcomplex (CDK7, MAT1, and cyclin H) is linked to the core via the XPD protein^[3] Two of the subunits, ERCC2/XPD and ERCC3/XPB, have helicase and ATPase activities and help create the transcription bubble. In a test tube these subunits are only required for transcription if the DNA template is not already denatured or if it is supercoiled.

Two other TFIIH subunits, CDK7 and cyclin H, phosphorylate serine amino acids on the RNA polymerase II C-terminal domain and possibly other proteins involved in the cell cycle. Next to a vital function in transcription initiation, TFIIH is also involved in nucleotide excision repair.

It is responsible for giving the 'go' signal which is why it is assembled last.

Functions

TFIIH is a general transcription factor that acts to recruit RNA PolII to the promoters of genes. It functions as a helicase that unwinds DNA. It also unwinds DNA after a DNA lesion has been recognized by either the global genome repair (GGR) pathway or the transcription-coupled repair (TCR) pathway of NER.^[4]

Trichothiodystrophy

Mutation in genes ERCC3/XPB, ERCC2/XPD or TTDA cause trichothiodystrophy, a condition characterized by photosensitivity, ichthyosis, brittle hair and nails, intellectual impairment, decreased fertility and/or short stature.^[5]

Disease

Genetic polymorphisms of genes that encode subunits of TFIIH (such as XPD and XPB) are known to be associated with increased cancer susceptibility in many tissues, e.g.; skin tissue, breast tissue and lung tissue . In addition to genetic variations, virus-encoded proteins also target TFIIH.^[6]

DNA repair

TFIIH participates in nucleotide excision repair (NER) by opening the DNA double helix after damage is initially recognized. NER is a multi-step pathway that removes a wide range of different damages that distort normal base pairing, including bulky chemical damages and UV-induced damages. Individuals with mutational defects in genes specifying protein components that catalyze the NER pathway, including the TFIIH components, often display features of premature aging^[5]^[7] (see DNA damage theory of aging).

References

↑ Reinberg, D, Flores (1992). "Factors involved in specific transcription by mammalian RNA polymerase II. Identification and characterization of factor IIH". J. Biol. Chem. 267, 2786–2793.
↑ Kim TK, Ebright RH, Reinberg D (2000). "Mechanism of ATP-dependent promoter melting by transcription factor IIH". Science. 288 (5470): 1418–22. PMID 10827951. doi:10.1126/science.288.5470.1418.
↑ Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annu. Rev. Genet. 34: 77–137. PMID 11092823. doi:10.1146/annurev.genet.34.1.77.
↑ Hoogstraten, D., Hoogstraten, D.; et al. (2002). "Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo". Mol. Cell 10, 1163–1174.
1 2 Theil AF, Hoeijmakers JH, Vermeulen W (2014). "TTDA: big impact of a small protein". Exp. Cell Res. 329 (1): 61–8. PMID 25016283. doi:10.1016/j.yexcr.2014.07.008.
↑ N., Le May; et al. (2004). "TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus". Cell 116, 541–550.
↑ Edifizi D, Schumacher B (2015). "Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms". Biomolecules. 5 (3): 1855–69. PMC 4598778 . PMID 26287260. doi:10.3390/biom5031855.

External links

Transcription Factor TFIIH at the US National Library of Medicine Medical Subject Headings (MeSH)

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA GCN4 HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1
(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1
(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2
(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)
(1.5) RF-X	RFX 1 2 3 4 5 6 ANK
(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR
subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX
subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ
subfamily 4	NUR NGFIB NOR1 NURR1
subfamily 5	LRH-1 SF1
subfamily 6	GCNF
subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2
(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX
(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4
(3.4) Heat shock factors	HSF 1 2 4
(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2
(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5
(4.2) STAT	STAT 1 2 3 4 5 6
(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63
(4.4) MADS box	Mef2 A B C D SRF
(4.6) TATA-binding proteins	TBP TBPL1
(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4
(4.9) Grainyhead	TFCP2
(4.10) Cold-shock domain	CSDA YBX1
(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1
(0.3) Pocket domain	Rb RBL1 RBL2
(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3
(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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